Throughout this application various publications are referenced by arabic numerals within parentheses. Full citations for these references may be found at the end of the specification immediately preceding the claims. The disclosures of these publications in their entireties are hereby incorporated by reference into this application in order to more fully describe the state of the art as known to those skilled therein as of the date of the invention described and claimed herein.
In 1975, Hamberg, Svensson and Samuelson (1) reported evidence for the existence of an unstable platelet-aggregating factor which they named thromboxane A.sub.2 (TXA.sub.2) and for which they proposed a novel bicyclic oxetane structure (A). A method for the preparation of the putative thromboxane A.sub.2 (TXA.sub.2) nucleus, an acid-labile 2,6-dioxa-[3.1.1]bicyloheptane, has been described (2). This method is now applied to the synthesis of TXA.sub.2 itself. TXA.sub.2 is an unstable substance T.sub.1/2 (37.degree. C.)=32 seconds in aqueous Krebs medium at pH 7.4) which is derived from the prostaglandin endoperoxide PGH.sub.2 and which is an important blood platelet aggregation factor. (1,3) Although TXA.sub.2 has not been previously isolated and characterized, its structure was proposed as A on the basis of its lability in neutral aqueous media, isotope incorporation experiments and the isolation of various TXB.sub.2 -like addition products. Structure A is prepared by the method of the present invention. ##STR3##
The synthetic material having structure A is indistinguishable from platelet-derived TXA.sub.2 in a variety of biological assays.